Our long-range goal is to obtain selective chemotherapeutics against cancer and DNA viruses by exploiting structural or conformational properties of isozymes peculiar to tumor or virus infected cells. To this aim we shall synthesize a series of novel aziridine and epoxide derivatives of pyrimidines and pyrimidine nucleosides as specific inhibitors of enzymes involved in nucleic acid metabolism. Some analogs are also potential affinity labeling agents or "suicide inhibitors", i.e., substrates whose potential for irreversible covalent binding is subject to bioactivation, and is accentuated following the initial interaction with the cognate enzyme. The selectivity of the target compounds in blocking specific enzyme activity will be evaluated with purified isozymes (thymidine kinase, 2'-deoxycytidine kinase and 2'-deoxycytidine deaminase) from normal and cancerous tissues and, in addition, in tissue cultures of malignant or virus infected cells.